PROJECT SUMMARY Cholera is a severe dehydrating illness of humans. It is endemic in over 50 countries and causes 3 to 5 million cases a year, resulting in approximately 100,000 deaths. Currently available cholera vaccines have shortcomings. They are often poorly immunogenic in children under the age of 5 years, and often do not induce robust long-term memory responses in immunologically nave populations. We provide strong preliminary data that antibodies targeting O-specific polysaccharide (OSP) affect Vibrio cholerae and are associated with protection against cholera. We here propose an international clinical study approach to investigate the impact of OSP-specific antibodies on V. cholerae.